Acute respiratory failure is a heterogeneous disorder that results in more than 300,000 Americans requiring admission to an intensive care unit for invasive mechanical ventilatory support each year. Though acute respiratory failure is a pulmonary disorder, patients who survive are not limited by respiratory symptoms after discharge. Rather persistent neuromuscular weakness is the primary disorder that adversely affects their quality of life and ability to function on a daily basis. Weakness in these survivors is related to the development of critical illness polyneuromyopathy (CIPNM). The ability to accurately diagnose CIPNM in these patients is difficult and often delayed. Presently, there is no available diagnostic screening test that accurately identifies those patients with acute respiratory failure that will develop CIPNM. Earlier and less invasive identification of critically ill patients that will eventually develop CIPNM may improve the efficacy of specific medical therapies, nutritional support, or intensive physical therapy. We have identified alterations on nerve conduction studies as early as three days after presentation to the hospital in critically ill patients. A progressive decrease over the subsequent seven days in the baseline amplitude was predictive of the development of CIPNM. In the first part of this proposal, we will prospectively determine whether changes on simple nerve conduction studies can be used as an effective diagnostic tool for the development of CIPNM in patients with acute respiratory failure. Presently, there are no therapies to treat the estimated 110,000 acute respiratory failure survivors who have developed CIPNM each year. Based on the results of our national surveys of physical therapists and intensive care physicians, the utilization and types of physical therapy for patients recovering from acute respiratory failure with neuromuscular weakness varies significantly depending on the type of hospital and primary diagnosis of the patient. In the second part of this proposal, we plan to perform a randomized, placebo controlled clinical trial to determine the effectiveness of an intensive four week physical therapy program for the subset of patients with acute respiratory failure who have developed CIPNM. This trial will determine the efficacy of the physical therapy programs that is currently performed in a non-evidence based manner for patients with acute respiratory failure across the United States. If successful, our studies would identify a novel way to diagnose patients with CIPNM and pave the way for a larger multi-center clinical trial of intensive physical therapy for survivors of acute respiratory failure. PUBLIC HEALTH RELEVANCE: and Relevance Acute respiratory failure is a heterogeneous disorder that results in more than 300,000 Americans requiring admission to an intensive care unit for invasive mechanical ventilatory support each year. Though acute respiratory failure is a pulmonary disorder, patients who survive their hospitalization are not limited by respiratory symptoms after discharge. Rather persistent neuromuscular weakness is the primary disorder that adversely alters their quality of life and ability to function on a daily basis. In this application we propose to identify a novel method of identifying those patients with acute respiratory failure that will develop neuromuscular weakness. In addition, we plan to conduct a randomized, placebo-controlled clinical trial called the Do It Now study (Diagnosis and Treatment of Neuromuscular Weakness) to determine the effectiveness of an intensive physical therapy program for patients recovering from acute respiratory failure who have developed neuromuscular weakness. This trial will establish the efficacy of the physical therapy programs that is currently performed for patients with acute respiratory failure in a non-evidence based manner across the United States.